Fluoroformates synthesis

Both aromatic and aliphatic fluoroformates 7 can be readily prepared from phenols or alcohols and carbonyl difluoride and treated with sulfur tetrafluoride without isolation. Hydrogen fluoride evolved in the reaction of hydroxy compounds with carbonyl di fluoride serves as a catalyst for the consecutive reaction with sulfur tetrafluoride.15<)-162 This provides a general, convenient, direct synthesis of aryl and alkyl trifluoromethyl ethers 5 from phenols and alcohols. When the intermediate fluoroformate 7 is isolated prior to treatment with sulfur tetrafluoride, at least one mole equivalent of hydrogen fluoride is necessary to promote the fluorination reaction. 159 163 Representative examples of the conversion of hydroxy compounds 6 into trifluoromethyl ethers 5 via intermediate fluoroformates 7 are given (for other examples 7 -> 5, see Houben-Weyl, Vol. E4, pp 628. 629). 

Aliphatic carbamates (readily available from alcohols and sodium cyanate)313 have also been submitted to fluorodediazoniation16,90 314 to give alkyl fluoroformates 890 which are useful tools in peptide synthesis and also valuable precursors of alkyl fluorides.315... 

There were not many new developments in the use of crown ethers for fluorination during the last decade, since the basicity of the fluoride anion is also enhanced along with the nucleophilicity. What is more, cheaper substitutes such as open-chain polyethers frequently led to similar results. However, there are still some reactions which are difficult to accomplish without these complexing agents and the synthesis of /-butyl fluoroformates... 

Scheme 24 Synthesis of rm-Butyl Fluoroformate from TrichlorofluoromethaneP ...

The reagents for the synthesis of Al -l-adamantyloxycarbonyl amino acid derivatives are similar to those used for other urethane-type protecting groups (Scheme 36). Although the related 1-adamantyl chloroformate (Adoc-Cl, 68) is obtained as crystalline solid, the acylation of amino acids under Schotten-Baumann conditions leads to significant decomposition of the reagent and thus its use does not result in satisfactory yields in all cases. Better results are obtained with 1-adamantyl fluoroformate (Adoc-F, 69) (yields of A -Adoc amino acids 85-95%)P I which is conunerciaUy available or readily prepared from adamantan-l-ol and... 

Furthermore, we succeeded in the preparation of FMOC-F (9-fluorenylmethyl fluoroformate) as a crystalline solid (mp. 41 °C). This reagent exhibits the same stability as FMOC-ONSu and can be easily shipped. Compared with FMOC-ONSu, FMOC-F gives similar to superior results in the protection of amines in peptides synthesis. 

In our continuing trials to extent the scope of the vinylic carbonates synthesis through the fluoroformate process, vinyl menthyl carbonate was obtained in excellent yield (80%) from menthyl fluoroformate. The polymer of vinyl menthyl carbonate was also proposed as menthol-release agent. It is noteworthy that this polymer can be easily prepared by reaction of menthyl fluoroformate with poly(vinyl alcohol) in DM50. 

Carbonyl difluoride is a particularly versatile fluorinating agent, and an important material for the synthesis of organofluorine compounds [1079], Its reactions with perfluoroalkenes gives perfluoroacyl fluorides in the presence of a fluoride ion source, and its facile reaction with amines or alcohols results in the formation of carbamoyl fluorides or fluoroformates, respectively. The fluorination of carbonyl compounds, such as aldehydes and ketones, with COF can give gem-difluorides by replacement of the carbonyl oxygen atom with two atoms of fluorine e.g.-. 

Scheme 2.30 Synthesis of selectively fluorinated aromatic compounds from phenols via the fluoroformate. Under optimized conditions, depending on the nature of the substituents X, the yields are nearly quantitative [80].

Peptide synthesis, N-protection Acetic-formic anhydride. Adamantyl chloroformate. Benzylthiocarbonyl chloride. /-Butoxycarbonyl-N-hydroxysuccinimide ester. /-Butyl azido-formate. /-Butylcarbonic diethylphosphoric anhydride. /-Butyl fluoroformate. /-Butyl oxycarbonyl fluoride. /-Butyl pentachlorophenyl carbonate. /-Butyl 2,4,5-trichlorophenyl carbonate. Carbobenzoxy chloride. 3,5-Dimethoxybenzyl p-nitrophenyl carbonate. [2-(Diphenyl)isopropyljphenyl carbonate. /-Pentyl chloroformate. 

Enzymatic synthesis offluorinated polyesters was demonstrated (133). Fluo-rinated diols such as 2,2,3,3-tetrafluoro-l,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pen tanediol were used as glycol substrate and polymerized with divinyl adipate using lipase CA catalyst. The enzymatic synthesis of polyester was also achieved in supercritical fluoroform solvent by the polymerization of bis(2,2,2-trichloroethyl) adipate and 1,4-butanediol (134). The molecular weight increased as a fiinction of the pressure. 

Atobe et al. reported that the electrochemical synthesis of polyp3rrole and polylhiophene was successfully proceeded in supercritical fluoroform [11]. Both the corresponding mOTiraners (pyrrole and thiophene) can be electropolymerized apparently faster in supercritical fluoroform than in the conventional organic media like an acetcMiitrile solution, and the obtained films have highly uniform structure (Fig. 2). 

Recently, 9-fluorenyhnethyl fluoroformate (Fmoc-F) was introduced as a cheap and effldent reagent that is now available in large quantities for the synthesis of Fmoc-amino adds [428, 429]. It is interesting to note that the good solubility of Fmoc-F permits the use of high concentration two-phase reaction conditions. As in the case of the Boc-F reaction, the addition of sodium borate after the addition of Fmoc-F prevents fluorine corrosion of the glassware. 

The Upase-catalyzed synthesis of polyesters was achieved in a supercritical fluid. The polymerization of bis(2,2,2-trichloroethyl) adipate and 1,4-butanediol using PPL catalyst proceeded in a supercritical fluoroform solvent to give a polymer with a molecular weight of several thousand [55]. By changing the pressure, the low-dispersity polymer fractions were separated. 

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